• Parasites, Hosts and Diseases
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• v.40 no.3
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• pp.119-129
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• 2002

Although there are many reports on the splenic (systemic) T cell response after Toxoptasma gondii infection, little information is available regarding the local T cell responses of peritoneal exudate cells (PEC) and gut intraepithelial Iymphocytes (IEL) following peroral infection with bradyzoites. Mice were infected with 40 cysts of the 76K strain of T. gondii, and then sacrificed at days 0, 1, 4, 7 and 10 postinfection (PI). The cellular composition and T cell responses of PEC and IEL were analyzed. The total number of PEC and IEL per mouse increased after infection, but the ratio of increase was higher in IEL. Lymphocytes were the major component of both PEC and IEL. The relative percentages of PEC macrophages and neutrophils/eosinophils increased signiflcantly at day 1 and 4 PI, whereas those of IEL did not change significantly. The percentage of PEC NK1.1 and ${\gamma\delta}T$ cells peaked at day 4 PI (p < 0.0001), and CD4 and $CD8{\alpha}T$ cells increased continuously after infection. The percentages of IEL $CD8{\alpha}$ and ${\gamma\delta}T$ cells decreased slightly at first, and then increased. CD4 and NK1.1 T cells of IEL did not change significantly after infection. $IFN-{\gamma}-producing$ PEC NK1.1 T cells increased significantly from day 1 PI, but the other T cell subsets produced $IFN-{\gamma}$ abundantly thereafter. The proportion of IEL $IFN-{\gamma}-producing$ $CD8{\alpha}$ and ${\gamma\delta}T$ cells increased significantly after infection, while IEL NK1.1 T cells had similar $IFN-{\gamma}$ production patterns. Taken together, CD4 T cells were the major phenotype and the important $IFN-{\gamma}$ producing T cell subsets in PEC after oral infection with T. gondii whereas $CD8{\alpha}T$ cells had these roles in IEL. These results suggest that PEC and IEL comprise different cell differentials and T cell responses, and according to infection route these factors may contribute to the different cellular immune responses.

• Molecules and Cells
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• v.42 no.3
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• pp.228-236
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• 2019

CD4 T cells differentiate into $ROR{\gamma}t/IL$-17A-expressing cells in the small intestine following colonization by segmented filamentous bacteria (SFB). However, it remains unclear whether SFB-specific CD4 T cells can differentiate directly from naïve precursors, and whether their effector differentiation is solely directed towards the Th17 lineage. In this study, we used adoptive T cell transfer experiments and showed that naïve CD4 T cells can migrate to the small intestinal lamina propria (sLP) and differentiate into effector T cells that synthesize IL-17A in response to SFB colonization. Using single cell RT-PCR analysis, we showed that the progenies of SFB responding T cells are not uniform but composed of transcriptionally divergent populations including Th1, Th17 and follicular helper T cells. We further confirmed this finding using in vitro culture of SFB specific intestinal CD4 T cells in the presence of cognate antigens, which also generated heterogeneous population with similar features. Collectively, these findings indicate that a single species of intestinal bacteria can generate a divergent population of antigen-specific effector CD4 T cells, rather than it provides a cytokine milieu for the development of a particular effector T cell subset.

• Molecules and Cells
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• v.26 no.1
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• pp.67-73
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• 2008

Herpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers $CD4^+$ T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in $CD4^+$ T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed $CD4^+$ T cells expressing CCR2 and CCR5. ExpreHerpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers $CD4^+$ T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in $CD4^+$ T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed $CD4^+$ T cells expressing CCR2 and CCR5. Expression of MCP-1 in the corneal stroma was confirmed in vivo. Finally, when HSV-1-primed $CD4^+$ T cells were adoptively transferred into wild type and MCP-1-deficient mice that had been sublethally irradiated to minimize chemokine production from immune cells, infiltration of $CD4^+$ T cells was markedly reduced in the MCP-1-deficient mice, suggesting that it is the MCP-1 from HSV-1-infected keratocytes that attracts $CD4^+$ T cells into the cornea.

• Journal of Pharmacopuncture
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• v.3 no.2
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• pp.79-97
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• 2000

Objectives : To investigate the effects of herb-acupunctures of Qi tonification herbs or formula on the rat immune depression induced by an anticancer drug, methotrexate (MTX) Methods: Animals were divided into 5 groups; Normal control group was not given any treatment. Immune depression was induced by oral administration of 1mg/kg MTX b.i.d for 4 days in Control, Sample I, II, and III groups. We treated on CV 4 (Guanyuan) with saline, Bojoongiggi-tang (Buzhongyiqi-tang), Ginseng Radix and Astragali Radix herb-acupunctures in Control, Sample I, II, and Ill groups, respectively. In both blood and spleen, the assessment of CD4+ T-cell count, CD8+ T-cell count, CD4/CD8 T-cell ratio was performed. Results: Here we show that 3 herb- acupuncture groups have an influence, to some extent, on CD4+ and CD8+ T-cell counts and CD4/CD8 T-cell ratio in both blood and spleen. Astragali Radix herb-acupuncture, in particular, was found to have significantly increased CD4+ T-cell count in blood and CD4/CD8 T-cell ratio in blood and spleen. Conclusions: The results of this study suggest that herb-acupunctures of Bojoongiggi-tang (Buzhongyiqi-tang), Ginseng Radix and Astragali Radix may have an influence over rat immune depression induced by MTX.

• Proceedings of the Microbiological Society of Korea Conference
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• 2008.05a
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• pp.62-64
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• 2008

A major hurdle to the development of RNA interference as therapy for HIV infection is the delivery of siRNA to T lymphocytes which are difficult cells to transfect even in vitro. We have employed a single chain antibody to the pan T cell surface antigen CD7 was conjugated to an oligo-9-arginine peptide (scFvCD7-9R) for T cell-specific siRNA delivery in NOD/SCIDIL2${\gamma}$-/- mice reconstituted with human peripheral blood lymphocytes (Hu-PBL). Using a novel delivery, we first show that scFvCD7-9R efficiently delivered CD4 siRNA into human T cells in vitro. In vivo administration to Hu-PBL mice resulted in reduced levels of surface CD4 expression on T cells. Mice infected with HIV-1 and treated on a weekly basis with scFvCD7-9R-siRNA complexes targeting a combination of viral genes and the host coreceptor molecule CCR5 successfully maintained CD4/CD3 T cell ratios up to 4 weeks after infection in contrast to control mice that displayed a marked reduction in CD4 T cell numbers. p24 antigen levels were undetectable in 3 of the 4 protected mice. scFvCD7-9R/antiviral siRNA treatment also helped maintain CD4 T cell numbers with reduced plasma viral loads in Hu-PBL mice reconstituted with PBMC from donors seropositive for HIV, indicating that this method can contain viral replication even in established HIV infections. Our results show that scFvCD7-9R could be further developed as a potential therapeutic for HIV-1 infection.

• Clinical and Experimental Pediatrics
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• v.53 no.2
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• pp.136-145
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• 2010

Natural killer T (NKT) cell is a special type of T lymphocytes that has both receptor of natural killer (NK) cell (NK1.1, CD161c) and T cell (TCR) and express a conserved or invariant T cell receptor called $V{\alpha}14J{\alpha}18$ in mice or Va24 in humans. Invariant NKT (iNKT) cell recognizes lipid antigen presented by CD1d molecules. Marine-sponge-derived glycolipid, ${\alpha}-galactosylceremide$ (${\alpha}-GalCer$), binds CD1d at the cell surface of antigen-presenting cells and is presented to iNKT cells. Within hours, iNKT cells become activated and start to secrete Interleukin-4 and $interferon-{\gamma}$. NKT cell prevents autoimmune diseases, such as type 1 diabetes, experimental allergic encephalomyelitis, systemic lupus erythematous, inflammatory colitis, and Graves' thyroiditis, by activation with ${\alpha}-GalCer$. In addition, NKT cell is associated with infectious diseases by mycobacteria, leshmania, and virus. Moreover NKT cell is associated with asthma, especially CD4+ iNKT cells. In this review, I will discuss the characteristics of NKT cell and the association with inflammatory diseases, especially asthma.

• Korean Journal of Veterinary Research
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• v.34 no.3
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• pp.441-446
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• 1994

The responsiveness of $CD8^+$ T-cell subpopulation according to serum-containing and serum-free conditions were investigated. Cells are freshly isolated from spleen of mature adult BALB/C mice between 13-20 weeks of age. $CD8^+$ T cells in serum-free conditions produce small amounts of IL-2, while significant amounts of IFNr following activation when compared the results of serum-containing conditions. These data indicate that serum-derived factors may play an important role in the alternations of $CD8^+$ T cell responsiveness.

• Biomedical Science Letters
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• v.27 no.4
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• pp.329-333
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• 2021

We previously identified that tumor cells genetically modified with a 4-1BBL co-stimulatory molecule had anticancer effects in a CT26 mouse colorectal tumor model. To identify the distinction between immune cells in a mouse tumor model treated with tumor cells genetically modified with 4-1BBL or β-gal, we examined the immune cells in CT26-WT, CT26-βgal, and CT26-4-1BBL tumor bearing mice 21 days after tumor cell administration. The CD8+ T cells population in mice treated with tumor cells genetically modified with 4-1BBL was significantly increased on day 21 compared to that of tumor cells genetically modified with β-gal in the spleen and tumor tissue. The CD4+ T cell population was not different between the two mice groups. The Foxp3+CD25^high CD4 T cell population decreased on day 21 in tumor tissues, but the decrease was not significant. We also found that CD8 T cells had pivotal roles in inhibiting tumor growth by treating mice with ant-CD4 and CD8 antibodies. These results suggest that tumor cells genetically modified with 4-1BBL could inhibit tumor growth by affecting on CD8 T lymphocytes.

• IMMUNE NETWORK
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• v.16 no.1
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• pp.13-25
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• 2016

Dendritic cells (DCs) are considered to play major roles during the induction of T cell immune responses as well as the maintenance of T cell tolerance. Naive CD4⁺ T cells have been shown to respond with high plasticity to signals inducing their polarization into effector/helper or regulatory T cells. Data obtained from in vitro generated bone-marrow (BM)-derived DCs as well as genetic mouse models revealed an important but not exclusive role of DCs in shaping CD4⁺ T cell responses. Besides the specialization of some conventional DC subsets for the induction of polarized immunity, also the maturation stage, activation of specialized transcription factors and the cytokine production of DCs have major impact on CD4⁺ T cells. Since in vitro generated BM-DCs show a high diversity to shape CD4⁺ T cells and their high similarity to monocyte-derived DCs in vivo, this review reports data mainly on BM-DCs in this process and only touches the roles of transcription factors or of DC subsets, which have been discussed elsewhere. Here, recent findings on 1) the conversion of naive into anergic and further into Foxp3^- regulatory T cells (Treg) by immature DCs, 2) the role of RelB in steady state migratory DCs (ssmDCs) for conversion of naive T cells into Foxp3⁺ Treg, 3) the DC maturation signature for polarized Th2 cell induction and 4) the DC source of IL-12 for Th1 induction are discussed.

• Korean Journal of Plant Resources
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• v.27 no.5
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• pp.567-575
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• 2014

Resveratrol is a naturally occurring stilbene which is safe and well-described compound with a potent anti-inflammatory activity. Recent studies suggested that resveratrol suppressed various inflammation mediated diseases such as asthma, chronic colitis, rheumatoid arthritis, and type 1 diabetes. These studies indicated that resveratrol might directly modulate $CD4^+$ helper T cells (Th cells)-mediated immune responses. However, it is not fully elucidated whether resveratrol directly regulates $CD4^+$ Th cell activation and differentiation. In the present study, $CD4^+$ Th cells were purified from C57BL/6 and treated with various concentrations of resveratrol. We found that resveratrol directly suppressed $CD4^+$ Th cells activation, leading to a defect in T cell proliferation. When $CD4^+$ Th cells were treated with resveratrol, cytokine production was also significantly reduced in a dose dependent manner. In accordance with these results, resveratrol even inhibited $CD4^+$ Th cells differentiation into Th1, Th2 or Th17, which produces IFN-${\gamma}$, IL-4 or IL-17 respectively. We also found that resveratrol could induce apoptosis of $CD4^+$ T cells at a high concentration. Our data demonstrated that resveratrol inhibited directly $CD4^+$ Th cells activation and differentiation. It suggests that resveratrol could be an efficient therapeutic strategy for autoimmune diseases in which $CD4^+$ Th cells play a critical role.